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PubMed2025

Finerenone and Cardiovascular Outcomes According to Baseline Kidney Function in Patients With Heart Failure: The FINEARTS-HF Trial.

BACKGROUND: Finerenone is known to reduce the risk of worsening heart failure (HF) events and cardiovascular (CV) death in patients with HF with mildly reduced or preserved ejection fraction. OBJECTIVES: The authors explored whether the benefit of finerenone among patients with HF with mildly reduced or preserved ejection fraction differs according to baseline measures of kidney function. METHODS: FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure) was a global, randomized clinical trial of finerenone vs placebo among patients with HF with mildly reduced or preserved ejection fraction. Finerenone was titrated to 20 mg/d if the estimated glomerular filtration rate (eGFR) was &#x2264;60 mL/min/1.73 m2 or 40 mg/d if eGFR was >60 mL/min/1.73 m2. The authors used a semiparametric proportional rates method, stratified by left ventricular ejection fraction (<60%; &#x2265;60%) and region, to assess for differential treatment effects on the composite of total HF events and CV death according to the baseline eGFR (continuous and categories [&#x2265;60 mL/min/1.73 m2, 45 to <60 mL/min/1.73 m2, <45 mL/min/1.73 m2] and urine albumin-creatinine ratio (UACR) (<30 mg/g, 30 to <300 mg/g, &#x2265;300 mg/g). RESULTS: The effect of finerenone to reduce the primary endpoint of total HF events and CV death did not significantly differ according to baseline eGFR (Pinteraction = 0.14 and 0.07 for continuous and categorical eGFR, respectively) with rate ratio 0.72 (95% CI: 0.59-0.88) for eGFR &#x2265;60 mL/min/1.73 m2, 0.83 (95% CI: 0.65-1.06) for eGFR 45 to <60 mL/min/1.73 m2, and 1.02 (95% CI: 0.83-1.26) for eGFR <45 mL/min/1.73 m2. The corresponding absolute event rates were 9.2 vs 12.5, 16.5 vs 19.9, and 28.0 vs 28.0 per 100 patient-years for finerenone vs placebo, respectively. Similar results were noted for total worsening HF events. Finerenone lowered the risk of the composite CV outcome similarly across baseline categories of UACR (Pinteraction = 0.48). CONCLUSIONS: In the FINEARTS-HF trial (where the target dose of finerenone was determined by baseline kidney function), the effect of finerenone to reduce the composite of cardiovascular death and total HF events did not significantly differ across a range of baseline eGFR and UACR.

Humans↗
PubMed2006

The AT2 gene may have a gender-specific effect on kidney function and pulse pressure in type I diabetic patients.

Diabetic nephropathy shows a higher incidence in male subjects, which may in part be owing to genetic factors. The angiotensin II type 2 receptor (AT2), present in the renal glomerulus, may oppose the deleterious effects of the type I receptor (AT1) through vasodilatation and growth inhibition. We determined whether the functional intronic G1675A or A1818T polymorphism of the X-chromosomal AT2 gene is associated with blood pressure levels or with kidney function. We genotyped 996 (538 female/458 male subjects) Finnish patients with type I diabetes from the FinnDiane-study in a cross-sectional study. DNA samples were amplified using standard polymerase chain reaction protocol and the genotypes were determined by the minisequencing method. Male patients with the AA haplotype had a lower glomerular filtration rate (83 +/- 32 vs 94 +/- 34 ml min(-1) 1.73 m(-2), P = 0.008) and a higher pulse pressure (PP) (62 +/- 18 vs 57 +/- 15 mm Hg, P = 0.002; P < 0.05 after adjustment for age) than did those with the GT haplotype. No differences between the genotypes or haplotypes and these variables were evident in females. In males, the G1675A was also an independent variable in a linear regression analysis with PP (r(2) = 0.16, coefficient=3.64, s.e.m.=1.38, P < 0.01) as the dependent variable. These data suggest a gender-specific association between the AT2 gene and kidney function and premature aging of the arterial tree in patients with type I diabetes.

Adult↗
PubMed1981

Strain differences in kidney function of inbred rats: 1. Glomerular filtration rate and renal plasma flow.

Bodyweight, kidney weight and glomerular filtration rate showed significant differences between strains--70% of the total variance was ascribed to the between-strain variance component--while the renal plasma flow showed only a slight strain difference due to a high within-strain variance component (63%). Heritability in the broad sense was 0.78 for bodyweight, 0.85 for kidney weight, 0.66 for glomerular filtration rate and 0.35 for renal plasma flow. There were significant genetic correlations between bodyweight and kidney weight (0.90), bodyweight and glomerular filtration rate (0.73), and between glomerular filtration rate and renal plasma flow (0.71), but not between kidney weight and kidney functions. Significant environmental correlations could be calculated only between bodyweight and all other variables, so that for comparison between strains it seems better to correct renal functions for bodyweight than for kidney weight, which would increase the variation of glomerular filtration rate.

Animals↗
PubMed1993

Changes in kidney function and faecal excretion of water and electrolytes with sodium chloride loading in sheep.

The renal and faecal routes of water and electrolyte excretion in sheep were compared and changes in kidney function assessed when similar amounts of sodium chloride (NaCl) were dosed in free and fixed ratios in water. Sheep (n = 6) either had free access to fresh drinking water (control phase) or 0.9% saline drinking water, or NaCl was dosed intraruminally with free access to fresh drinking water. In the final phase of the investigation, sheep were dosed intraruminally with NaCl while water intake was restricted. Variables monitored included fresh or saline water intake, water, sodium and potassium loss via the urine and faeces, glomerular filtration rate (GFR), fractional excretions of sodium (FENa) and potassium (FEK) and solute free water clearance (CH2O). Results indicated that where NaCl intake was high, sodium excretion via the urine was of far greater importance than that via the faeces and that changes in kidney function which occurred in order to excrete excess sodium, included increases in GFR and FENa, and declines in FEK and CH2O. Where significant differences were obtained in variables between the phases of high salt intake, these were attributed to differences in sodium absorption from the gastrointestinal tract. It was concluded that when NaCl intake is high, sodium homeostasis is chiefly maintained by increasing the amount of sodium made available to the nephron tubule (increased GFR), by decreased tubular reabsorption of this sodium and by increasing solute free water reabsorption.

Animals↗